ABSTRACT Alcohol-related health problems include highly prevalent and serious disorders such as hypertension, diabetes, and depression. Substantial evidence supports a J-shaped relationship between alcohol use and diabetes1, whereas a linear relationship is well-documented between alcohol use and hypertension2, and there is mixed evidence regarding the shape of the relationship between alcohol use and depression3,4. A common biologic mechanism for alcohol's effects on these disorders may be inflammation. Inflammation is a general response by the immune system to harm, such as bodily injury or exposure to irritants (e.g. alcohol)5. Inflammation that becomes chronic, potentially lasting for years, is associated with an increased risk of health problems6, including hypertension, diabetes, and depression7. Thus, intervening on inflammation offers new opportunities for prevention and treatment. However, the mechanisms of inflammation in the context of alcohol use and health require further study. Racial/ethnic health disparities are especially relevant in this context because racial/ethnic minorities share a disproportionately large portion of the burden caused by these disorders8. Moreover, recent studies show racial/ethnic minorities have consistently higher levels of inflammation9, and these differences have been observed across the lifespan10,11. The overall objective of this K01 Career Development Award is to provide the principal investigator, Dr. Martinez, with the skills necessary to conduct alcohol research that bridges social, behavioral, and physiological domains. The research activities proposed under this award will lead to a better understanding of alcohol use and inflammation as mechanisms contributing to alcohol-related racial/ethnic health disparities. In turn, findings will inform the development and implementation of a subsequent R01-funded longitudinal investigation of immunologic mechanisms and associated factors that may explain differential drinking patterns and related physical and mental health outcomes among racial/ethnic minorities. Upon completion of study activities, Dr. Martinez will be poised for a productive career as an independent, NIH-funded scientist. Dr. Martinez is trained as an alcohol researcher with a strong background in the biological sciences and expertise in alcohol epidemiology, particularly the comorbidity between alcohol use and depression. Dr. Martinez's long-term goal is to become a successful NIH-funded scientist with expertise in the relationships between biologic mechanisms and alcohol-related racial/ethnic health disparities. She is proposing a combination of didactic and applied research activities, under the mentorship of experts in the field led by her primary mentor Dr. Sarah Zemore, to provide her with the following skills necessary to accomplish this goal: (1) expertise in the role of inflammation in mental and physical health, (2) expertise in racial/ethnic disparities in the effects of alcohol on mental and physical health, (3) longitudinal statistical modeling techniques, and (4) field methods in epidemiologic and biomarker data collection. The proposed research activities consist of two studies (A & B) with two aims each. Study A is a secondary analysis of data from Waves I-V of the National Longitudinal Study of Adolescent to Adult Health (AddHealth). Study B entails primary pilot data collection via self-administered dried blood spots (saDBS) from a subsample of the 2020 National Alcohol Survey (NAS). Study A, Aim I: To describe the longitudinal relationships between alcohol use, inflammation, and health outcomes (hypertension, diabetes, and depression). Dr. Martinez will accomplish this aim by: (a) examining the individual associations between alcohol use and inflammation and health with prospective data from AddHealth, and (b) testing inflammation as a mediator of the relationships between alcohol use and each health outcome. Study A, Aim II: To describe how race/ethnicity impacts alcohol's effects on health via inflammation and the roles of environmental stressors and unhealthy behaviors. Dr. Martinez will accomplish this aim by: (a) testing whether the effects of alcohol use on inflammation and health are stronger among racial/ethnic minorities compared to Whites, and (b) testing whether environmental factors and health behaviors mediate the effect of race/ethnicity on the relationships between alcohol use and inflammation and health. Study B, Aim I: To pilot test the use of a novel biosample collection method (self-administered dried blood spots (saDBS)). Dr. Martinez will accomplish this aim by: (a) assessing the acceptability and feasibility of saDBS among a sample of NAS participants, and (b) assessing the participant's experience of completing a saDBS sample. Study B, Aim II: To explore additional immune markers relevant to the relationships between alcohol use, inflammation and health across racial/ethnic groups in a nationally representative adult sample. Dr. Martinez will accomplish this aim by: (a) exploring immune markers beyond those included in Study A using the NAS, and (b) exploring associations between these immune markers and alcohol use and health across racial/ethnic groups. These research activities will culminate in the submission of an R01 as part of NIAAA's Health Disparities Initiative to study prospectively the effect of immunological mechanisms on alcohol-related health outcomes across racial/ethnic groups. The career development and research activities proposed in this K01 application will lay the foundation for Dr. Martinez's career as a successful, independent, NIH-funded scientist.